Today, concerns about manufacturing costs and process times are at the forefront of fiscal budgets, and improving formulations is on every company's agenda. "Nowadays, smaller tablets are the advantage, and if you need less active ingredient, you are happy because then you need less excipients to formulate it." Not only do patients want to swallow smaller tablets, but if the capacity of process equipment determines the batch size, then there are more smaller tablets in a batch, which means less batch documentation, smaller packaging, less volume for transportation, and so forth. "Nowadays, these issues count," says Folttmann. "Excipients that perform their functions at lower concentration so that less material needs to be handled have a good chance of success in the marketplace."
Functionality and QbDThe US Food and Drug Administration's quality-by-design (QbD) initiative has changed the way excipient suppliers develop, characterize, and manufacture their materials. "We have seen some benefits of implementing QbD into the pharmaceutical manufacturing process, including a reduction in approval delays, a more streamlined approval process and an easier course for implementing postapproval changes," says Nandu Deorkar, director of research and development, laboratory and pharmaceutical products at Mallinckrodt Baker (Phillipsburg, NJ). "However, the concept of QbD can present implementation opportunities and challenges to both raw-material (excipient) suppliers and pharmaceutical manufacturers. As a part of the QbD system, raw-material characteristics and their variability on the process and product quality or performance should be studied and documented. As such, raw materials must be well-characterized and developed using QbD principles to reduce variability"
Engineering and coprocessing are additional sophisticated tools that can help excipient suppliers enhance their materials to the high-quality level demanded by drug makers. "QbD initiatives require well-characterized and highly functional excipients to enable their implementation by drug formulators," says Deorkar. "Excipient technology development is centered on particle engineering and new chemical entities." For example, Mallinckrodt Baker recently developed "PanExcea" performance excipients, spherical homogeneous particles for immediate-release oral dosage forms and orally disintegrating tablet forms, using a proprietary particle engineering technology. This technology enables the precise tailoring of physical attributes such as particle size, distribution, porosity, and density in homogeneous particles containing multiple components, without changing the chemistry. "This reduces unfavorable attributes, while enhancing the functional characteristics of individual components through synergistic effects," says Deorkar.